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. 2008 Mar;29(3):471-7.
doi: 10.1016/j.neurobiolaging.2006.10.018. Epub 2006 Nov 28.

Resetting of central and peripheral circadian oscillators in aged rats

Alec J Davidson  1 , Shin Yamazaki, Deanna M Arble, Michael Menaker, Gene D Block
Affiliations

Resetting of central and peripheral circadian oscillators in aged rats

Alec J Davidson et al. Neurobiol Aging. 2008 Mar.

Abstract

The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To determine whether the dynamic behavior of circadian oscillators is also affected by aging we studied the resetting behavior of the Period1 transcriptional rhythm of peripheral and central oscillators in response to a 6h advance or delay in the light schedule. We employed a transgenic rat with a luciferase reporter to allow for real-time measurements of transcriptional rhythmicity. While phase resetting in the SCN following an advance or a delay of the light cycle appears nearly normal in 2-year-old rats, resynchronization of the liver was seriously disrupted. In addition, the arcuate nucleus and pineal gland exhibited faster resetting in aged rats relative to 4-8-month-old controls. The consequences of these deficits are unknown, but may contribute to organ and brain diseases in the aged as well as the health problems that are common in older shift-workers.

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Figures

Figure 1
Figure 1
Resynchronization of SCN and liver Per1-luc rhythms after phase-shifts A. Phase shift schedules. Asterisks indicate the times at which cultures were prepared for Per1-luc measurements. B. Typical examples of bioluminescence recordings from liver cultures prepared either before the shift, or on the first or 6th day following a phase-delay. The arrows indicate the peaks used as phase markers for subsequent analysis of rhythm phase. C. Peak-phases of SCN and liver cultures during resynchronization in young and aged rats. The phases from unshifted rats were normalized to 0, and subsequent phase measurements plotted relative to those baselines. The vertical dotted lines indicate the target phases that the tissues are moving towards. Students t-test; *p<0.05 relative to young controls.
Figure 2
Figure 2
Resynchronization of Pineal gland and arcuate nucleus Per1-luc rhythms after phase-shifts in young and aged rats. Conventions are the same as in Fig. 2. Student's t-test; *p<0.05 and ** p<0.002 relative to young controls.
See this image and copyright information in PMC

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